Ars Pharmaceuticals, Inc. · NASDAQ:SPRY
Ars Pharmaceuticals — Silverback Therapeutics — Investor Presentation (September 2021)
35 slides from Ars Pharmaceuticals's investor presentation, Sep 16, 2021
Slide 1: Silverback Therapeutics Corporate Presentation September 2021
Exhibit 99.1 SILVERBACK THERAPEUTICS Corporate Presentation September 2021
Slide 2: Forward-looking statements and disclaimers
Forward-looking statements and disclaimers Any reproduction or distribution of this presentation, in whole or in part, or the disclosure of any of its contents is prohibited. This presentation includes certain forward-looking statements that involve risks and uncertainties that could cause actual re
Slide 3: Corporate highlights
Corporate highlights ImmunoTAC conjugates are designed to unlock a new class of targeted immuno-oncology agents that direct a 1 myeloid cell agonist to the tumor microenvironment for localized activation Emerging clinical data supports proof-of-mechanism for localized TLR8 agonism and the ImmunoTAC
Slide 4: Pipeline of systemically delivered, tissue-targeted programs with milestones over next 6-18 months
Advancing a pipeline of systemically delivered, tissue-targeted programs with value-generating milestones expected over the next 6-18 months Asset / Targeting Payload Antigen Indication(s) Preclinical Studies Phase 1 Phase 2 Anticipated Milestones • 4Q 2021 – Initiate Libtayo tumor-specific expansio
Slide 5: ImmunoTAC platform pairs antigen binding domains with linker-payloads
ImmunoTAC platform strategically pairs antigen binding domains with linker-payloads to modulate pathways underlying serious diseases Library of Proprietary Molecules Antigen Binding Domains Antigen binding domain HER2 Nectin4 ASGR1 Undisclosed Linker-payload Linker-Payloads Fc region TLR8 TGFbR Undi
Slide 6: SBT6050 localizes TLR8 activation of myeloid cells in tumors via HER2 antibody
SBT6050 is designed to localize TLR8 activation of myeloid cells in tumors via a HER2 antibody TUMOR CELL Antigen Binding Domain: anti-HER2 antibody (pertuzumab) HER2 HER2 FcγR FcγR HER2+ MYELOID CELL NSCLC Tumor Administered systemically through Payload: TLR8 agonist SC injection TLR8 Fc region: Ig
Slide 7: TLR8 is highly expressed in human myeloid cell types
TLR8 is highly expressed in human myeloid cell types that elicit anti-tumor responses when activated TLR8 Agonism Direct Effects Indirect Effects Macrophages Dendritic Cells Myeloid Derived Monocytes NK Cells T Cells B Cells Suppressor Cells Direct tumor killing Promote anti-tumor Reprogramming to a
Slide 8: Proof-of-mechanism established in patient dose escalation study
Proof-of-mechanism established in 40 patient dose escalation study* SBT6050 ▪ Pharmacodynamic (PD) markers indicative of myeloid and T/NK cell activation generally increase with dose, plateauing at 0.6 mg/kg ▪ PD activity is maintained with repeat dosing ▪ SBT6050 payload detected in intratumoral ma
Slide 9: Phase 1/1b dose escalation study design
Phase 1/1b dose escalation study; projected RP2D determined for expansion cohorts Part 1: monotherapy dose escalation Part 2: monotherapy tumor specific cohorts SBT6050 SC injection Q2W SBT6050 SC injection Q2W HER2-expressing (IHC 2+ or 3+) or HER2-amplified advanced cancers expressing HER2 BC, gas
Slide 10: SBT6050 immune activation may enhance effectiveness of Libtayo
SBT6050 activation of innate and adaptive immune response may enhance and expand the effectiveness of Libtayo 1 SBT6050 activates myeloid cells, including dendritic cells, which then recruit and activate anti-tumor T cells Induction of myeloid cell activation along with increases in immune cell infi
Slide 11: Combination with Enhertu and Tukysa + Herceptin supported by scientific rationale
Combination with Enhertu and with Tukysa + Herceptin +/- capecitabine are supported by a strong scientific and clinical rationale Enhertu | Herceptin+Tukysa +/- capecitabine Combination with SBT6050 Drive immunogenic tumor cell death and » Activates DCs, potentially enhancing presentation of neoanti
Slide 12: Clinical development plans beyond monotherapy
Clinical development plans beyond monotherapy Combination regimen Strategic Initiative (estimated start) 3L+ mBC 2L+ NSCLC Combine with foundational IO therapy to lay Libtayo 3L+ GEA Accelerated approval in late line settings 3L+ GEA groundwork in early lines of treatment (4Q21) 2L+ NSCLC Enhertu 2L
Slide 13: SBT6050 combination potentially unlocking large market opportunities
SBT6050 is designed to be used in combo with SOC agents such as CPIs and/or trastuzumab-based agents, potentially unlocking large market opportunities Estimated U.S. Incidence of Early-Line Estimated U.S. Incidence of Relapsed or HER2-Expressing Patients Refractory HER2-Expressing Patients 90,000 12
Slide 14: SBT6050 alone or with pembrolizumab has a manageable safety profile
SBT6050 administered alone or in combination with pembrolizumab has a manageable safety profile Most frequent* treatment-related treatment emergent adverse events (TEAEs), by maximum severity Part 1: SBT6050 Monotherapy (n=32) Part 3: SBT6050 + Pembrolizumab (n=8) Grade 1 Grade 2 Grade 3 Grade 1 Gra
Slide 15: PK studies reflect saturation of HER2-mediated clearance
PK studies reflect saturation of HER2-mediated clearance at dose levels ≥ 0.6 mg/kg and conjugate stability Serum PK Profiles Dose-proportional increases in AUC at doses ≥ 0.6 mg/kg SBT6050 dose (mg/kg) AUC (mg*d/mL) Fold increase 0.15 + pembro 0.10 ± 0.17 ~15.7x 0.3 + pembro 1.57 ± 1.19 0.3 1.16 ±
Slide 16: Induction of PD biomarkers of myeloid cell activation
Induction of PD biomarkers of myeloid cell activation observed across all dose levels and generally plateau at 0.6 mg/kg IP-10 MCP-1 IL-6 5000 3000 30000 20000 4000 2000 10000 3000 1000 1000 2000 75 1000 50 25 0 0 0 Part 1: SBT6050 Monotherapy Part 3: SBT6050 + pembrolizumab 0.3 mg/kg 0.9 mg/kg 0.15
Slide 17: Induction of IFNg biomarker of T and NK cell activation
Induction of IFNg, a biomarker of T and NK cell activation, observed across all dose levels and generally plateaus at 0.6 mg/kg Activation of DCs in lymph nodes drives expansion of IFNg polyfunctional tumor reactive T cells 1500 Lymph Node Tumor 1000 500 Dendritic cell 200 150 100 Antigen (from tumo
Slide 18: PD activity is maintained with repeat dosing
PD activity is maintained with repeat dosing IP-10 MCP-1 IL-6 6000 3000 8000 2000 6000 4000 4000 1000 2000 2000 75 50 1000 25 0 0 0 IFNg 600 Part 1: SBT6050 Monotherapy Part 3: SBT6050 + pembrolizumab 0.3 mg/kg 0.9 mg/kg 0.15 mg/kg + 400 mg pembro 400 0.6 mg/kg 1.2 mg/kg 0.30 mg/kg + 400 mg pembro 2
Slide 19: SBT6050 payload detected on tumor cells and in intratumoral macrophages
SBT6050 payload is detected on tumor cells and in intratumoral macrophages, supporting the proposed mechanism of action in the TME SBT6050 payload is detected on tumor cells and in intratumoral macrophages of patients dosed at 0.6 mg/kg HER2 IHC 1+ breast cancer HER2 IHC 3+ breast cancer 19SBT6050 p
Slide 20: Early signals of anti-tumor activity in prioritized tumor types
SBT6050 demonstrated early signals of anti-tumor activity in tumor types prioritized for expansion cohorts Part 1: SBT6050 monotherapy Part 3: SBT6050 + pembrolizumab 0.3 mg/kg 0.9 mg/kg 0.15 mg/kg + 400 mg pembro 0.6 mg/kg 1.2 mg/kg 0.3 mg/kg + 400 mg pembro Figure includes patients with tumor type
Slide 21: Adverse events do not change with repeat dosing; PR maintained
Adverse events do not change with repeat dosing; PR maintained while off study Partial Response 1 Stable Disease Progressive Disease Non-Evaluable Time Off-Study Part 1: SBT6050 monotherapy 0.3 mg/kg 0.9 mg/kg 0.6 mg/kg 1.2 mg/kg Part 3: SBT6050 combination with pembrolizumab 0.15 mg/kg + 400 mg pem
Slide 22: SBT6050 conferred clinical benefit to heavily pre-treated patients
SBT6050 conferred clinical benefit to patients with heavily pre-treated, advanced solid tumors NSCLC Breast Cancer Bladder Cancer Breast Cancer Breast Cancer Gastric Cancer HER2 IHC 2+ HER2 IHC 3+ HER2 IHC 2+ HER2 IHC 3+ HER2 IHC 3+ HER2 IHC 3+ Not amplified Amplification unknown 67F 73F 60M 48F 40F
Slide 23: Data support a projected RP2D of 0.6 mg/kg
Safety profile, PK, and PD data support a projected RP2D of 0.6 mg/kg At the 0.6 mg/kg dose level: ✓ Safety and tolerability profile consistent with an immune activator and manageable ✓ Serum PK suggests HER2 target saturation ✓ Pharmacodynamic markers indicative of myeloid, T/NK cell activation rea
Slide 24: SBT6290 comprises the same TLR8 agonist linker-payload conjugated to Nectin4 antibody
SBT6290 comprises the same TLR8 agonist linker-payload used in SBT6050, SBT6290 conjugated to a proprietary Nectin4-directed monoclonal antibody ▪ Nectin4 is a clinically validated target by Seagen through the 2019 accelerated approval of ADC enfortumab vedotin (Padcev) in bladder cancer ▪ SBT6290 i
Slide 25: SBT6290 is selective for Nectin4 and blocks TIGIT:Nectin4 interaction
SBT6290 is selective for Nectin4 and blocks TIGIT:Nectin4 interaction SBT6290 is Selective for Nectin4 SBT6290 binding domain blocked TIGIT binding to Nectin4-expressing tumor cells Nectin Family Members Binding Affinity Nectin4 <1 pM 100 Nectin1 No binding detected; affinity is 75 Nectin2 >1µM Nect
Slide 26: SBT6290 activates human myeloid cells in a Nectin4- and Fc-dependent manner
SBT6290 activates human myeloid cells in a Nectin4- and Fc-dependent manner SBT6290 Activity is Nectin4-Dependent SBT6290 Activity Requires Fc Engagement pos neg Nectin4 cell line Nectin4 cell line pos Nectin4 cell line 26SBT6290 activates human myeloid cells in a Nectin4- and Fc-dependent manner SB
Slide 27: SBT6290-S demonstrates robust single agent activity in vivo
SBT6290-S demonstrates robust single agent activity in vivo Nectin4-Expressing EMT6 Mouse Model Isotype Control (10 mg/kg) Unconjugated Nectin4 mAb (10 mg/kg) SBT6290-S (10 mg/kg) 1500 1500 1500 1000 1000 1000 500 500 500 0 0 0 0 7 14 21 28 35 42 49 56 0 7 14 21 28 35 42 49 56 0 7 14 21 28 35 42 49
Slide 28: Nectin4 overexpressed across bladder, TNBC, H&N, and NSCLC
Nectin4 is overexpressed in bladder, TNBC, H&N, and NSCLC, among other indications, unlocking a large opportunity in an untapped market Nectin4 Overexpression Across Select Tumor Types 101,000 58,000 48,000 21,000 10,000 11,000 3,000 2,000 181k estimated early-line U.S. cases per year Bladder TNBC H
Slide 29: SBT8230 liver-localized TLR8 agonism for chronic hepatitis B
SBT8230 provides opportunity to further realize potential of SBT8230 TLR8 agonism with liver-localized activity, if approved ▪ Potent IFNγ-mediated immune response and seroconversion, which TLR8 agonism has been shown to drive, is key determinant of achieving a functional cure in cHBV ▪ Clinical val
Slide 30: ASGR1-TLR8 potently activated human myeloid cells
ASGR1-TLR8 potently activated human myeloid cells, resulting in a robust IFNg response TNFa: Myeloid Activation, Potent IFNγ Activation Increased Viral Ag Presentation 90000 15000 10000 Lead conjugate Unconjugated mAb 60000 5000 Control conjugate 0 0.01 0.1 1 10 100 1000 30000 Concentration (nM) IL-
Slide 31: ASGR1-S reduces HBsAg and drives seroconversion in mouse model
ASGR1-S reduces Hepatitis B surface antigen (HBsAg) and drives seroconversion in AAV-HBV mouse model HBsAg plasma levels Seroconversion p= < 0.0001 p= 0.02 ASGR1-S lowered average plasma viral DNA titers 2.5 logs 31ASGR1-S reduces Hepatitis B surface antigen (HBsAg) and drives seroconversion in AAV-
Slide 32: Multiple preclinical programs to expand ImmunoTAC platform
Multiple preclinical programs to expand ImmunoTAC platform IO TLR8 Programs ▪ Two additional undisclosed IO targets may enable us to expand coverage of solid tumor indications ▪ Same TLR8 linker-payload utilized in SBT6050 and SBT6290 and similar in vitro functional profile Liver-Directed TGFβRi Imm
Slide 33: Led by a veteran team with a track record of advancing therapies
Led by a veteran team with a track record of advancing transformative therapies Leadership Team Board of Directors Peter Thompson, MD Co-Founder, Chairman Vickie Capps Rob Hershberg, MD, PhD Laura Shawver, PhD Valerie Odegard, PhD Naomi Hunder, MD Jonathan Piazza Chief Executive Officer President, C
Slide 34: Corporate highlights
Corporate highlights ImmunoTAC conjugates are designed to unlock a new class of targeted immuno-oncology agents that direct a 1 myeloid cell agonist to the tumor microenvironment for localized activation Emerging clinical data supports proof-of-mechanism for localized TLR8 agonism and the ImmunoTAC
Slide 35: Silverback Therapeutics
SILVERBACK’ THERAPEUTICS,
Silverback Therapeutics — Investor Presentation (September 2021) on 6ix